Polymorphism of NLRP3 Gene and Association with Susceptibility to Digestive Disorders in Rabbit
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NLR family pyrin domain containing 3 (NLRP3) is a key component of the inflammasome, whose assembly is a crucial part of the innate immune response. The aim of the present study was to evaluate the association between exon 3 polymorphisms of NLRP3 and the susceptibility to digestive disorders in rabbits. In total, five coding single-nucleotide polymorphisms (cSNPs) were identified; all of which are synonymous. Among them, c.456 C> and c.594 G> were further genotyped for association analysis based on case-control design (n =162 vs n =102). Meanwhile, growing rabbits were experimentally induced to digestive disorders by feeding a fiber-deficient diet, subsequently they were subjected to mRNA expression analysis. Association analysis revealed that haplotype H1 (the two cSNPs: GT) played a potential protective role against digestive disorders (p<0.001). The expression of NLRP3 in the group H1HX1 (H1HX1 is composed of H1H1, H1H3 and H1H4) was the lowest among four groups which were classified by different types of diplotypes. Those results suggested that the NLRP3 gene was significantly associated with susceptibility to digestive disorders in rabbit.
Abstract
NLR family pyrin domain containing 3 (NLRP3) is a key component of the inflammasome, whose assembly is a crucial part of the innate immune response. The aim of the present study was to evaluate the association between exon 3 polymorphisms of NLRP3 and the susceptibility to digestive disorders in rabbits. In total, five coding single-nucleotide polymorphisms (cSNPs) were identified; all of which are synonymous. Among them, c.456 C> and c.594 G> were further genotyped for association analysis based on case-control design (n =162 vs n =102). Meanwhile, growing rabbits were experimentally induced to digestive disorders by feeding a fiber-deficient diet, subsequently they were subjected to mRNA expression analysis. Association analysis revealed that haplotype H1 (the two cSNPs: GT) played a potential protective role against digestive disorders (p<0.001). The expression of NLRP3 in the group H1HX1 (H1HX1 is composed of H1H1, H1H3 and H1H4) was the lowest among four groups which were classified by different types of diplotypes. Those results suggested that the NLRP3 gene was significantly associated with susceptibility to digestive disorders in rabbit.
참고문헌 (34)
- -processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder, "Immunity", 2004, 319~325
- Andoh, A., "Recent advances in molecular approaches to gut microbiota in inflammatory bowel disease", Curr. Pharm. Des, 15, pp.2066~2073 (2009)
- Bauer, C., "Colitis induced in mice with dextran sulfate sodium (DSS) is mediated by the NLRP3 inflammasome", Gut, 59, pp.1192~1199 (2010)
- Bennegadi, N., "Impact of fibre deficiency and sanitary status on non-specific enteropathy of the growing rabbit", Anim. Res, 50, pp.401~413 (2001)
- Comeron, J. M, "Selective and mutational patterns associated with gene expression in humans : Influences on synonymous composition and intron presence", Genetics, 167, pp.1293~1304 (2004)
- Cummings, J., "The genetics of NOD‐like receptors in Crohn's disease", Tissue Antigens, 76, pp.48~56 (2010)
- Dowds, T. A., "Cryopyrin-induced interleukin 1 secretion in monocytic cells", J. Biol. Chem, 279, pp.21924~21928 (2004)
- Dupaul-Chicoine, J., "Control of intestinal homeostasis, colitis, and colitis-associated colorectal cancer by the inflammatory caspases", Immunity, 32, pp.367~378 (2010)
- Eady, S., "Heritability of resistance to bacterial infection in meat rabbits", Livest. Sci, 112, pp.90~98 (2007)
- Garreau, H., "Genetic parameters of production traits and resistance to digestive disorders in a commercial rabbit population", Proc. 9th World Rabbit Congr, pp.10~13 (2008)
- Gidenne, T., "A comprehensive approach of the rabbit digestion: consequences of a reduction in dietary fibre supply", Livest. Prod. Sci, 64, pp.225~237 (2000)
- Goymer, P., "Synonymous mutations break their silence", Nat. Rev. Genet, 8, pp.92~ (2007)
- Hirota, S. A., "NLRP3 inflammasome plays a key role in the regulation of intestinal homeostasis", Inflamm. Bowel Dis, 17, pp.1359~1372 (2011)
- Kanneganti, T. D., "Intracellular NOD-like receptors in host defense and disease", Immunity, 27, pp.549~559 (2007)
- Kastbom, A., "Genetic variation in proteins of the cryopyrin inflammasome influences susceptibility and severity of rheumatoid arthritis(the Swedish TIRA project)", Rheumatology, 47, pp.415~417 (2008)
- Lamkanfi, M., "Caspase-1 inflammasomes in infection and inflammation", J. Leukoc. Biol, 82, pp.220~225 (2007)
- Li, Z., "A partition-ligation-combination-subdivision EM algorithm for haplotype inference with multiallelic markers: update of the SHEsis", Cell Res, 19, pp.519~523 (2009)
- Liu, H., "Hardy-Weinberg equilibrium in genetic epidemiology. Zhong nan da xue xue bao. Yi xue ban= Journal of Central South University", Med Sci, 35, pp.90~93 (2010)
- Mariathasan, S., "Inflammasome adaptors and sensors: intracellular regulators of infection and inflammation", Nat. Rev. Immunol, 7, pp.31~40 (2007)
- Martinon, F., "Inflammatory caspases and inflammasomes: master switches of inflammation", Cell Death Differ, 14, pp.10~22 (2006)
- Ott, J, "Association of genetic loci", Neurology, 63, pp.955~958 (2004)
- Pétrilli, V., "The inflammasome: a danger sensing complex triggering innate immunity", Curr. Opin. Immunol, 19, pp.615~622 (2007)
- Roberts, R., "Evidence of interaction of CARD8 rs2043211 with NALP3 rs35829419 in Crohn's disease", Genes Immun, 11, pp.351~356 (2010)
- Rosell, J., "Health status of commercial rabbitries in the Iberian peninsula. A practitioner’s study during 2002", World Rabbit Sci, 11, pp.157~169 (2002)
- Royet, J., "Detection of peptidoglycans by NOD proteins", Trends Cell Biol., 13(12), pp.610~614 (2003)
- Sauna, Z. E., "Understanding the contribution of synonymous mutations to human disease", Nat. Rev. Genet, 12, pp.683~691 (2011)
- Schoultz, I., "Combined polymorphisms in genes encoding the inflammasome components NALP3 and CARD8 confer susceptibility to Crohn's disease in Swedish men", Am J Gastroenterol, 104, pp.1180~1188 (2009)
- Sharp, P. M., "Codon usage in regulatory genes in Escherichia coli does not reflect selection for ‘rare’codons", Nucleic Acids Res, 14, pp.7737~7749 (1986)
- Stephens, M., "A new statistical method for haplotype reconstruction from population data", Am. J. Hum. Genet, 68, pp.978~989 (2001)
- Ting, J. P. Y., "CATERPILLERs, pyrin and hereditary immunological disorders", Nat. Rev. Immunol, 6, pp.183~195 (2006)
- Vandesompele, J., "Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes", Genome Biol, 3 (2002)
- Villani, A. C., "Common variants in the NLRP3 region contribute to Crohn's disease susceptibility", Nat. Genet, 41, pp.71~76 (2008)
- Zhang, G. W., "A reduced incidence of digestive disorders in rabbits is associated with allelic diversity at the TLR4 locus", Vet. Immunol. Immunopathol, 144, pp.482~486 (2011)
- Zheng, S. L., "Sequence variants of toll-Like receptor 4 are associated with prostate cancer risk", Cancer Res, 64, pp.2918~ (2004)
